Key clinical-trial evidence for nivolumab

In December 2014, the US Food and Drug Administration (FDA) granted accelerated approval for the use of nivolumab (OPDIVO®; Bristol-Myers Squibb; USA) in the treatment of melanoma based on positive results of a multicentre, randomised trial that established the superiority of nivolumab over standard therapy in adult patients with unresectable or metastatic melanoma.

Nivolumab is a monoclonalantibody that binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2, thereby releasing PD-1 pathway-mediated inhibition of the immune response, including anti-tumour immune response.

Nivoluamb is approved for the treatment of patients with melanoma who have been previously treated with the anti-CTLA-4 inhibitor ipilimumab and, for patients with melanoma with BRAF V600 mutations who have progressed after treatment with ipilimumab and a BRAF inhibitor (eg vemurafenib or dabrafenib).

Clinical trial experience

CheckMate-037: efficacy

FDA approval was based on objective response rate (ORR) and durability of response in the first 120 patients in an ongoing randomised, open-label trial of 370 patients with unresectable or metastatic melanoma treated with nivolumab 3 mg/kg intravenously every 2 weeks (n=268) or investigator choice of chemotherapy (n=102).

All patients had a minimum of 6 months follow-up.

Chemotherapy included either dacarbazine 1000 mg/m2 every 3 weeks or the combination of carboplatin AUC (area under curve) 6 every 3 weeks plus paclitaxel 175 mg/m2 every 3 weeks.

Patients were excluded from the trial if they had an autoimmune disease, a medical condition that required corticosteroids or immunosuppression, or a history of severe ipilimumab-related adverse reactions.

Patients with unresectable or metastatic melanoma were required to have disease progression after treatment with ipilimumab, and a BRAF inhibitor if BRAF V600 mutation positive.

Patients were treated until disease progression or unacceptable toxicity.

Median time on therapy was 5.3 months in the nivolumab arm and 2 months in the chemotherapy arm.

The major efficacy endpoints were confirmed ORR as measured by blinded independent central review using Response Evaluation Criteria in Solid Tumours (RECIST v1.1) and response duration.

CheckMate-066: efficacy and adverse events

The purpose of this study is to compare the clinical benefit, as measured by duration of overall survival, of nivolumab vs. dacarbazine in subjects with previously untreated, unresectable or metastatic melanoma.

At 1 year, the overall rate of survival was 72.9% (95% confidence interval [CI], 65.5 to 78.9) in the nivolumab group, compared with 42.1% (95% CI, 33.0 to 50.9) in the dacarbazine group (P<0.001).

The median progression-free survival was 5.1 months in the nivolumab group versus 2.2 months in the dacarbazine group (hazard ratio for death or progression of disease, 0.43; 95% CI, 0.34 to 0.56; P<0.001).

The objective response rate was 40.0% (95% CI, 33.3 to 47.0) in the nivolumab group versus 13.9% (95% CI, 9.5 to 19.4) in the dacarbazine group (odds ratio, 4.06; P<0.001).

In both the PD-L1 positive and PD-L1 negative/indeterminate subgroups, nivolumab-treated patients had improved OS vs dacarbazine.

Nivolumab was associated with significant improvements in overall survival and progression-free survival, compared with dacarbazine, among previously untreated patients who had metastatic melanoma without a BRAF mutation.

The most common nivolumab treatment-related adverse events were fatigue (20%), pruritus (17%), and nausea (16.5%).

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The New Zealand approved datasheet is the official source of information for this prescription medicine, including approved uses and risk information. Check the New Zealand datasheet on the Medsafe website.